Long-term analysis of ABI auditory performance in patients with neurofibromatosis type 2-related schwannomatosis.

PURPOSE: This retrospective monocentric study aimed to evaluate long-term auditory brainstem implant (ABI) function in patients with neurofibromatosis type 2, and to investigate the prognostic factors for ABI use. METHODS: Between 1997 and 2022, 27 patients with at least five years of follow-up underwent implantation with 32 ABIs. At 1- and 5-years post-implantation and at last follow-up, ABIs were classified as used or non-used and the size of the ipsilateral tumor was recorded. For patients who used their ABIs, we assessed speech perception (disyllabic words, MBAA sentences) in quiet conditions with the ABI only, by lip-reading (LR), and with a combination of the two (ABI + LR). Hearing improvement was calculated as Δ ABI = (ABI + LR)-LR scores. Predictive factors for ABI use were analyzed. RESULTS: One year post-implantation, 74% patients were ABI-users and 66% of the ABIs were used. Two of these patients were non-users at five years, and another two at last follow-up (14 ± 5.2 years); 54% of the patients were ABI-users at last follow-up. Δ ABI revealed a hearing improvement of 32-41% (disyllabic words) and 28-37% (MBAA sentences). Among 16 ABIs with at least LR improvement at 1-year post-implantation, 4 decreased their performance, coinciding with a large growing ipsilateral tumor in 3/4 ABIs. We identified no significant prognostic factors for ABI use. CONCLUSIONS: ABIs are indicated in case of bilateral deafness with a non-functional cochlear nerve. Half the patients with ABIs used their implants and auditory performance remained stable over time, except in cases of ipsilateral tumor growth.

Cochlear Implantation in Neurofibromatosis Type 2-Related Schwannomatosis: Long-Term Hearing Outcomes.

OBJECTIVE: To evaluate long-term hearing outcomes following cochlear implantation in patients with neurofibromatosis type 2 and ipsilateral vestibular schwannoma. STUDY DESIGN: Retrospective study. SETTING: Tertiary general hospital. METHODS: Twenty-two patients undergoing cochlear implantation between 2004 and 2018 with at least 1 year of follow-up were included. Patients were categorized as "users" or "nonusers" of their cochlear implant (CI). For users, speech perception (disyllabic words) without lip-reading was assessed in quiet conditions 1-year postimplantation, and annually thereafter. CI users were classified into 2 groups on the basis of speech intelligibility (≥40% or <40%). Demographic data, treatment options, and tumor size were also recorded. RESULTS: One year after implantation, 16 (73%) patients used their CI daily. Twelve of these patients had a speech intelligibility ≥40% (mean: 74 ± 21.9%). Three had a Koos stage IV tumor. At the last visit (mean duration of follow-up: 6 ± 5 years), 12 of these 16 patients were still using their implant daily, and 6 had a speech intelligibility ≥40%. No predictive factors for good performance at 1 year or performance stability were identified. CONCLUSION: Neurofibromatosis type 2 is a complex disease profoundly affecting patient quality of life, and cochlear implantation should always be considered on a case-by-case basis. In some individuals, cochlear implantation can provide good speech intelligibility for extended periods, even posttreatment or in cases of large tumors.

An unusual finding of an anaplastic meningioma in NF2-related schwannomatosis.

NF2-related schwannomatosis (NF2) is a rare autosomal-dominant genetic disorder characterized by bilateral vestibular schwannomas and multiple meningiomas. This case report presents the extremely rare occurrence of an anaplastic meningioma in a 12-year-old male with previously undiagnosed NF2. The patient presented with a history of abdominal pain and episodic emesis, gait unsteadiness, right upper and lower extremity weakness, and facial weakness. He had sensorineural hearing loss and wore bilateral hearing aids. MR imaging revealed a sizable left frontoparietal, dural-based meningioma with heterogeneous enhancement with mass effect on the brain and midline shift. Multiple additional CNS lesions were noted including a homogenous lesion at the level of T5 indicative of compression of the spinal cord. The patient underwent a frontotemporoparietal craniotomy for the removal of his large dural-based meningioma, utilizing neuronavigation and transdural ultrasonography for precise en bloc resection of the mass. Histopathology revealed an anaplastic meningioma, WHO grade 3, characterized by brisk mitotic activity, small-cell changes, high Ki-67 proliferation rate, and significant loss of P16. We report an anaplastic meningioma associated with an underlying diagnosis of NF2 for which we describe clinical and histopathological features.

A simplified technique for correction of complete ptosis secondary to palpebral neurofibromatosis.

PURPOSE: To present a simplified technique in management of complete ptosis secondary to neurofibromatosis. METHODS: This prospective, non-comparative, clinical interventional study included 13 patients with complete ptosis secondary to histologically proved plexiform neurofibromas. It was conducted at the Orbital Unit of Assiut University Hospital, the referral center of Upper Egypt in the period between June 2013 and October 2021. In all cases, a simplified technique of 5 surgical steps was applied: (A) Division of the involved eyelid surgically into three parts by drawing 2 curvilinear lines, the superior line 11 mm below and parallel to the lower eyebrow hairline and the inferior one 10 mm above the lid margin, (B) Resection (full-thickness) of the large middle part which involves the main pathology and lies between the 2 lines, (C) Preservation of the upper part with identification, dissection and clamping of the levator muscle, (D) Refinement of the lower part by removal of any tissue between the skin and the debulked tarsus and (E) Re-suturing of the upper and lower parts in layers; conjunctiva to conjunctiva, levator to tarsus (after resection of a part that corrects the ptosis) and skin to skin. RESULTS: Ptosis was completely corrected in 8 cases (61.5%) and residual mild ptosis occurred in 5 patients (38.5%). No exposure keratopathy or tumor growth was reported during the follow-up period of minimum 1 year. CONCLUSIONS: This simplified technique could be considered as a surgical basis for correction of complete ptosis in neurofibromatosis.

Stereotactic Radiosurgery and Radiotherapy for Vestibular Schwannoma in NF2-Related Schwannomatosis.

OBJECTIVES: To determine the long-term control rates and hearing outcomes for growing vestibular schwannoma in NF2-related schwannomatosis (NF2) treated with stereotactic radiosurgery (SRS) and fractionated radiotherapy (FRT). METHODS: Retrospective review of all patients treated with SRS/FRT between 1986 and2021 from a tertiary NF2 unit. Overall tumor control was defined as: (1) growth control (growth failure was defined as growth in any dimension of 3 millimetres or more from baseline post-SRS/FRT), and (2) treatment control (no need for further intervention). Loss of serviceable hearing was defined as a drop in speech discrimination score below 50% after SRS/FRT. RESULTS: There were 81 cases, with a mean duration of follow-up of 125 months. Overall control rate was 72% (58/81), with 80% (65/81) growth control and 74% (60/81) treatment control. There was a 5-year actuarial survival of 77% and 10-year survival of 71%. Forty-three percent (30/69) of cases did not have serviceable hearing at baseline. Of those remaining, 49% (19/39) preserved serviceable hearing during follow-up at a mean of 106 months. Actuarial survival for preservation of serviceable hearing at 5 and 10 years was 69% and 53%. There were poorer outcomes with increasing genetic severity, and with baseline tumor size >3 cm. No cases of SRS/FRT-related malignancy were identified at a mean follow-up of 10 years. CONCLUSION: Stereotactic radiosurgery/fractionated radiotherapy are an effective option to treat growing vestibular schwannoma in patients with NF2 with the potential for hearing preservation in a proportion of patients. LEVEL OF EVIDENCE: 4-Case Series Laryngoscope, 134:2364-2371, 2024.

A case report of giant malignant schwannoma of the sciatic nerve associated with neurofibromatosis-1: A CARE-compliant article.

RATIONALE: Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome that causes multiple central and peripheral nerve sheath tumors. People with NF1 have a 10% chance of developing malignant peripheral nerve sheath tumors (MPNSTs). Here we report a unique instance of a malignant schwannoma that has remained free of metastasis since its initial removal a decade ago. The malign schwannoma has been infrequently documented in the literature, and remarkably, no instances of such an extensive postoperative time without metastases have ever been described. PATIENT CONCERNS: A 46-year-old male patient with NF had multiple neurofibromas in different parts of his body, underwent surgery about 10 years ago (2013), and was diagnosed histopathologically as MPNST. DIAGNOSES: He was admitted to our institution with a recurrent mass in the posterior third of the proximal thigh and severe pain radiating to the left lower extremity, which presented as sciatic pain (2021). A magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography examination revealed that the tumor was likely malignant. INTERVENTIONS: Surgical excision was performed. OUTCOME: A 10-year follow-up revealed no metastases or neurologic impairment. LESSONS: When articles about benign schwannomas are placed in a separate category, little is written about NF-1-related malignant schwannomas of the sciatic nerve. MPNSTs are high-grade, aggressive sarcomas with a high risk of local recurrence (40%-65%) and metastasis to other body parts. Therefore, among the various benign peripheral nerve sheath tumors in NF-1 patients, the diagnosis of MPNST is crucial.Orthopedic surgeons should be aware that neurofibromas in NF-1 have a significant risk of developing MPNSTs. This study reports the successful treatment of a giant malignant sciatic nerve schwannoma with a long follow-up period without metastasis.

SRS for Vestibular Schwannomas - Current Status.

Stereotactic radiosurgery (SRS) is an established modality of treatment for vestibular schwannomas (VS). We aim to summarize the evidence-based use of SRS in VSs and address the specific considerations pertaining to the same, along with our own clinical experiences. A thorough review of the literature was done to gather evidence regarding the safety and efficacy of SRS in VSs. Additionally, we have reviewed the senior author's experience in treating VSs (N = 294) between 2009 and 2021 and our experiences with microsurgery in post-SRS patients. Available scientific evidence upholds the role of SRS in VSs, in small-to-medium-sized tumors (5-year local tumor control >95%). The risk of adverse radiation effects remains minimal, while the hearing preservation rates are variable. Our center's post-GammaKnife VS follow-up cohort (sporadic - 157, neurofibromatosis-2 - 14) showed excellent tumor control rates at the last follow-up of 95.5% (sporadic) and 93.8% (neurofibromatosis-2), with a median margin dose of 13 Gy and mean follow-up periods of 3.6 (sporadic) and 5.2 (neurofibromatosis-2) years. Microsurgery in post-SRS VSs poses a formidable challenge due to the resulting thickened arachnoid and adhesions to critical neurovascular structures. Near-total excision is the key to better functional outcomes in such cases. SRS is here to stay as a trusted alternative in the management of VSs. Further studies are required to propose means of accurate prediction of hearing preservation rates and also to compare the relative efficacies of various SRS modalities.

Targeted Therapies in the Treatment of Vestibular Schwannomas: Current State and New Horizons.

Vestibular schwannomas continue to cause hearing loss, facial nerve paralysis, imbalance, and tinnitus. These symptoms are compounded by germline neurofibromatosis type 2 (NF2) gene loss and multiple intracranial and spinal cord tumors associated with NF2-related schwannomatosis. The current treatments of observation, microsurgical resection, or stereotactic radiation may prevent catastrophic brainstem compression but are all associated with the loss of cranial nerve function, particularly hearing loss. Novel targeted treatment options to stop tumor progression include small molecule inhibitors, immunotherapy, anti-inflammatory drugs, radio-sensitizing and sclerosing agents, and gene therapy.

Schwannomatosis of the sciatic nerve: a case report.

Schwannomas are one of the most common peripheral nerve sheath neoplasms. These tumors, which are characteristically slow-growing and encapsulated, can occur in solitary or multiple forms. Although they usually occur sporadically, they can be seen with various genetic tumor predisposition syndromes such as neurofibromatosis type 2 (NF-2) or schwannomatosis. However, schwannomatosis is a relatively rare disease. We present a case of a 22-year-old patient with segmental schwannomatosis of the sciatic nerve and a comprehensive literature review.

Segmental Schwannomatosis of the Lower Extremity - A Case Series.

Segmental schwannomatosis involving a nerve in single limb is uncommon. Schwannomatosis is used to describe a distinct clinicopathological disease of multiple schwannomas without manifestations of neurofibromatosis, and it is termed segmental when a single extremity is involved. Surgery is indicated when there is progressive clinical deterioration or progressive increase in size of the tumors. We present a case series of segmental schwannomatosis involving the lower limb.

Clinical features of multiple spinal schwannomas without vestibular schwannomas.

BACKGROUND: Multiple spinal cord tumors in a single patient are very rare and most often seen in cases of neurofibromatosis and associated disorders. Schwannomatosis, which is characterized by the development of multiple schwannomas without vestibular schwannomas, has been newly defined as a distinct form of neurofibromatosis. The purpose of the present study was to describe and review the clinical and radiological features and the management of patients with multiple spinal schwannomas without vestibular schwannomas. METHODS: Between 1986 and 2016, 19 patients with multiple spinal schwannomas without vestibular schwannoma were diagnosed and treated. Of the 19 patients, 13 were males, and 6 were females. The mean age at the first surgery for spinal schwannoma was 45.2 years old. The mean follow-up period was 123.4 months. The clinical features and radiological findings of the patients with multiple spinal schwannomas were retrospectively reviewed. RESULTS: Among the 19 patients, there were more than 140 spinal schwannomas. The most common area of spinal schwannoma was the thoracolumbar-lumbar region. Initial symptoms and chief complaints caused by spinal schwannomas were primarily pain in the trunk or extremities in 17 (89.5%) of 19 patients. More than 60 spinal schwannomas were surgically resected. Multiple spinal surgeries were required in six patients. In all 19 patients, surgical treatment has provided successful relief of symptoms and neurological recovery. CONCLUSIONS: Surgical treatment was safe and effective in patients with multiple spinal schwannomas without vestibular schwannomas. After surgery, we recommend that all patients be followed with magnetic resonance imaging to monitor for asymptomatic tumors or detect new tumors early.

Status and Recommendations for Incorporating Biomarkers for Cutaneous Neurofibromas Into Clinical Research.

OBJECTIVE: To summarize existing biomarker data for cutaneous neurofibroma (cNF) and to inform the incorporation of biomarkers into clinical trial design for cNFs. METHODS: The cNF working group, a subgroup of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) consortium, was formed to review and inform clinical trial design for cNFs. Between June 2018 and February 2020, the cNF working group performed a review of existing data on genetic biomarkers for cNFs in the setting of neurofibromatosis type 1. We also reviewed criteria for successful biomarker application in the clinic. The group then held a series of meetings to develop a consensus report. RESULTS: Our systematic literature review of existing data revealed a lack of validated biomarkers for cNFs. In our report, we summarize the existing signaling, genomic, transcriptomic, histopathologic, and proteomic data relevant to cNF. Finally, we make recommendations for incorporating exploratory aims for predictive biomarkers into clinical trials through biobanking samples. CONCLUSION: These recommendations are intended to provide both researchers and clinicians with best practices for clinical trial design to aid in the identification of clinically validated biomarkers for cNF.

ABI-auditory brainstem implant.

The Auditory Brainstem Implant (ABI) is based on the classic cochlear implant (CI) but uses a different stimulation electrode. At MED-EL, the early development activities on ABI started in the year 1994, with the suggestion coming from J. Helms and J. Müller from Würzburg, Germany in collaboration with the Univ. of Innsbruck Austria. The first ABI surgery in a neuro-fibromatosis (NF2) patient with the MED-EL device took place in the year 1997. Later, the indication of ABI was expanded to non-NF2 patients with severe inner-ear malformation, for whom a regular CI will not be beneficial. Key translational research activities at MED-EL in collaboration with numerous clinics investigating the factors that affect the hearing performance amongst ABI patients, importance of early ABI implantation in children, tools in pre-operative assessment of ABI candidates and new concepts that were pursued with the MED-EL ABI device. The CE-mark for the MED-EL ABI to be used in adults and children down to the age of 12 months without NF-2 was granted in 2017 mainly based on two long-term clinical studies in the pediatric population. This article covers the milestones of translational research from the first concept to the widespread clinical use of ABI in association with MED-EL.

Neurofibromatosis and a Portrait of 1 in 3000.

Neurofibromatosis, a genetic disorder that occurs in 1 in 3000 births, can cause tumors to grow anywhere on or in the body. The first author (RM), an artist-researcher and mother of a son living with neurofibromatosis, has painted and exhibited more than 200 portraits of people living with neurofibromatosis to raise awareness of and resources for this little-known disorder. Among many stories shared through RM's works is the story of Ashok, a Nepali man who has undergone 3 surgeries to remove facially disfiguring tumors that developed as a result of neurofibromatosis. This article analyzes portraits of Ashok and interviews that the senior author (RI) conducted with Ashok and RM during each phase of his surgical process to present a case study of their lived experience at the intersection of art and medicine that illustrates the power of portraiture as medicine.

Surgical management of peripheral nerve sheath tumours in children, with special consideration of neurofibromatoses.

INTRODUCTION: Peripheral nerve sheath tumours in children are a rare and heterogeneous group, consisting mostly of benign tumours as well as malignant neoplasms. Especially in the paediatric population, diagnostics and indication for therapy pose relevant challenges for neurosurgeons and paediatric neurologists alike. Most paediatric cases that need surgical intervention are associated to neurofibromatosis type 1 (NF1). METHODS: We retrospectively reviewed all paediatric cases treated at the Department of Neurosurgery in Tübingen between 2006 and 2017 for peripheral nerve sheath tumours. We analysed clinical signs, symptoms, histology, association to an underlying phacomatosis and sensory/motor function. RESULTS: Of the 82 identified patients, the majority had NF1 (76.8%). Nine children bore a sporadic tumour without underlying phacomatosis (11%), 8 had NF2 (9.8%) and 2 schwannomatosis (2.4%), A total of 168 surgical interventions were performed, and 206 tumours were removed. Indication for surgery was in most instances significant tumour growth (45.2%) followed by pain (33.9%). New deficits led to surgery in 12.5% of interventions; malignancy was suspected in 8.3%. Histopathology revealed mostly neurofibromas (82.5%), divided into cutaneous neurofibromas (10.7%), infiltrating plexiform neurofibromas (25.7%) and peripheral nerve-born neurofibromas (46.1%). 12.1% of tumours were schwannomas, 2.9% MPNST, 1.5% ganglioneuroma (n = 3) and 1 hybrid-neurofibroma and perineurinoma each. Leading symptoms, such as pain and motor and sensory deficits, improved after 125/166 interventions (74.4%), remained unchanged following 39 interventions (23.2%) and worsened in 4 occasions (2.4%). CONCLUSION: Surgery is safe and effective for (neurofibromatosis associated) peripheral nerve sheath tumours in the paediatric population; however, management needs a multidisciplinary setting. We propose early surgical resection in paediatric patients with peripheral nerve sheath tumours with significant growth, or pain, or motor deficit, or suspected malignancy.

Germline Mutations for Novel Candidate Predisposition Genes in Sporadic Schwannomatosis.

BACKGROUND: Schwannomatosis is a late-onset tumor predisposition syndrome associated with the development of many different types of malignancies. A relevant genetic mechanism can be explained by three mutational events. The first-hit mutation is a germline mutation, and the SMARCB1 mutation on chromosome 22 is the most well-known genetic abnormality in patients with schwannomatosis. LZTR1 is another major predisposing gene in 22q-related schwannomatosis that lacks SMARCB1 variants. Although these two variants account for the occurrence of most familiar schwannomatoses, the genetic causes of sporadic schwannomatosis for the most part remain unknown. Therefore, current molecular diagnostic criteria cannot completely explain the basis of this disease. The common genetic background between schwannomatosis and other related malignant tumors is also unclear. Moreover, it is not easy to explain various clinical manifestations by only two known mutations. QUESTION/PURPOSES: (1) Are there important sequences outside the SMARCB1 or LZTR1 region on chromosome 22 that might carry a first-hit mutational predisposition to sporadic schwannomatosis? Or are there alternative evolutionarily conserved loci that might carry a first-hit mutational predisposition? (2) Is the age of disease onset associated to such genetic variants? METHODS: This study was a retrospective chart review and prospective genetic study on patients with schwannomatosis who were treated surgically. The clinical criteria to diagnose schwannomatosis were as follows: (1) histologically proven nonvestibular schwannomas; (2) no evidence of vestibular schwannomas on 3-mm brain MRI. A total of 21 patients were treated between March 2006 and June 2015. Since nine patients did not visit the outpatient clinic during the recruitment period, we obtained blood samples from 12 patients with schwannomatosis for a genetic analysis. After two patients were excluded because of their family history of schwannomatosis, genetic analyses were finally performed on 10 patients. Then, those with NF2, SMARCB1 or LZTR1 variants were screened by whole exome sequencing. All 10 patients passed our screening strategy. There were eight men and two women, with a median (range) age of 43 years (24 to 66) at the time of diagnosis. To select candidate genes, common ethnic variants and frequent mutations in in-house exome sequencing data were removed to exclude the population-specific polymorphisms not found in other population and to generalize the findings. Frameshift, nonsense, and splice-site variants were deemed pathogenic. Missense variants were classified as potentially pathogenic, variants of uncertain significance, or benign using in silico (via computer simulation) prediction algorithms, Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping v2 (PolyPhen-2), and Combined Annotation Dependent Depletion (CADD). A variant was considered potentially pathogenic if two or more algorithms predicted the variant to be damaging and benign if none considered it damaging. Then, potentially pathogenic variants only in the genes associated with cancer-predisposition or DNA damage repair were classified as the pathogenic candidate variants of sporadic schwannomatosis. The predictions for pathogenic candidate variants were checked again on Clinical Interpretation of Genetic Variants (InterVar) based on the American College of Medical Genetics guidelines and validated against Mendelian clinically applicable pathogenicity scores (M-CAP scores). RESULTS: We detected 26 variants; 13 variants across 10 genes were predicted to be pathogenic and found in seven patients, two each in ARID1A, PTCH2, and NOTCH2 and one each in MSH6, ALPK2, MGMT, NOTCH1, CIC, TSC2, and CDKN2A. One frameshift deletion in PTCH2 met the criteria for pathogenic or likely pathogenic classification, as recommended by the American College of Medical Genetics guidelines. Six missense mutations were classified as possibly pathogenic variants based on M-CAP scores. Four predicted pathogenic missense variants were detected in DNA damage repair (DDR) genes. Three DDR genes were affected: ARID1A, MGMT, and MSH6. Among the nine predicted pathogenic mutations detected in known cancer-predisposing genes, one was a frameshift deletion and the others were missense mutations. Seven tumor suppressor genes were involved: PTCH2, ALPK2, CIC, NOTCH1, NOTCH2, TSC2, and CDKN2A. One patient with multiple pathogenic variants in two DDR genes, ARID1A and MSH6, received a schwannomatosis diagnosis at 33 years old. Each of the other patients who had single variants in the DDR gene received their diagnoses at 41 years of age. The age at diagnosis was 40 years or older in patients with variants in cancer-predisposing genes, except for one patient who had multiple variants in TSC2 and CDKN2A. The carrier of those variants received the diagnosis at 24 years old. CONCLUSIONS: This study identified first-hit candidate mutations predisposing patients to schwannomatosis that were not related to SMARCB1 or LZTR1 variations in a cohort of patients with sporadic schwannomatosis. Patients with sporadic schwannomatosis without SMARCB1 or LZTR1 genetic variation may have developed the disease because of genomic variants related to cancer initiation in areas other than chromosome 22. Seven of 10 patients had predicted pathogenic germline mutations in DDR and cancer predisposition genes. We detected multiple cancer-related mutations in each patient. The age at the time schwannomatosis was diagnosed might be associated with a combination of variants and characteristics of the genes containing the variants; however, we did not have enough patients to confirm this association. CLINICAL RELEVANCE: The germline mutations identified in this study and the ideas related to the age of disease onset may provide potential candidate variants for future research on sporadic schwannomatosis and help to revise the current clinical and molecular diagnostic criteria. Further in vivo and in vitro studies are needed for these variants.

Recurrent Schwannomatosis of the Hand.

Background: Peripheral nerve sheath tumors (PNSTs) are neoplastic soft tissue masses generated from the abnormal proliferation of Schwann cells. Often, these tumors occur in isolation and are known as schwannomas or neurilemmomas. The presence of multiple schwannomas is known as schwannomatosis. The purpose of this article is 2-fold: (1) to review the relevant literature and describe a unique case of this rare condition; and (2) to emphasize salient clinical considerations in the diagnosis and treatment of schwannomatosis. Methods: In this report, we describe the case of a 52-year-old white man who presented with multiple recurrent soft tissue masses of the right hand. On initial presentation, he described pain across his right hand and index finger, which persisted despite numerous prior operations. The index finger had a flexion contracture around the location of the proximal interphalangeal joint, and there were multiple tender masses along the length of the finger and palm. Results: Segmental excision of the affected radial digital nerve was performed. A pulp flap based on contralateral neurovascular bundle resulted in a sensate, pain-free digit. Tissue pathology confirmed the diagnosis of multiple neurilemmomas. Conclusions: We report the success of a radial digital neurectomy in a patient with widespread neurilemmomas, who had previously excluded that painful digit from use. It was through careful consideration of the preoperative differential diagnosis, by valuing the preoperative imaging, and by considering all surgical options with specific attention paid to skin flap design that this good outcome of a fully sensate, pain-free, mobile index finger was achieved.

[A Case of Familial Schwannomatosis Occurring as Intraorbital Schwannoma].

A 67-year-old male presenting with left exophthalmos and progressive visual disturbance was referred to our department. Tumors at the supraclavicular fossa and dorsal femoral region were resected at ages 27 and 45 years. His father and son had both been diagnosed with spinal tumors, and his son's tumor was pathologically diagnosed as a schwannoma. Brain MRI of his son demonstrated no intracranial tumor. Brain MRI of the patient revealed a multilobular tumor of 2 cm diameter compressing the optic nerve medially within the left muscle cone, and no other intracranial tumors. However, large masses lateral to the pharynx and intercostal nerve, as well as multiple spinal tumors were detected. Transcranial total resection of the intraorbital tumor was performed. The pathological diagnosis was consistent with a schwannoma. These clinical characteristics fulfilled the diagnostic criteria of familial schwannomatosis. The postoperative course was uneventful. His visual dysfunction and eye movement disorder resolved completely. The intraorbital tumor was believed to originate from the lacrimal nerve. Sequencing of all exons for SMARCB1 and LZTR1 using DNA extracted from the tumor did not reveal any mutations. This case is the third report on familial schwannomatosis in Japan.